1. Field of the Invention
The present invention relates to a method for compensation of the potential drift of a reference electrode in electrochemical measurements of concentrations of at least one dissolved chemical entity in a liquid medium and also to an improved method for measuring the oxygen concentration in a liquid medium and an apparatus to be used with this method using a reference electrode, a working electrode and a counter electrode. The invention also relates to a pacemaker comprising an apparatus according to the invention and the use of a method according to the invention in a pacemaker or the like.
2. Description of the Prior Art
The terms listed below as used herein have the following definitions:
Measuring potential: the applied potential, as related to a reference potential, during the measurement, in the description denoted E.
Measuring voltage: used in algorithms denoted U, which are part of the present invention.
Floating potential: the potential, as related to a reference potential, an electrode will acquire when placed in an electrolyte and no current is allowed to pass through an outer circuit, i.e. not passing through the electrolyte, in the description denoted E0.
It should be understood that these potentials actually refer to an arbitrarily chosen level, e.g. common ground.
Chemical entity: a chemical entity is defined for the purpose of this application as either a gas or a chemical substance or compound dissolved in a liquid medium.
Such entities can be subjected to analysis by electrolytic reduction/oxidation reactions and the corresponding reduction/oxidation potential, or rather the electric current evoked by said potentials for characterizing the amount and substance reduced/oxidized.
Working electrode: herein and below relates to the electrode at the surface of which the reduction of the chemical entity takes place.
Sensor rate: A calculated rate increase to be added to a basic pacing rate when the sensor is used in an active implant. The sensor herein and below being an oxygen sensor comprising a working electrode and a counter electrode and a reference electrode.
In modern medicine, implantable heart pacemakers are used increasingly for the therapy of heart arrhythmia. It is a well-known fact that physical demands on the body require levels of oxygen adapted to the degree of physical activity to be delivered to the body. Thus the body activity lowers the venous oxygen concentration in the blood as a function of the degree of activity. The oxygen concentration in the blood and the changes in the concentration may be used as indicators for a change in the stimulation pulse rate in order to regulate the rate of the stimulation pulses emitted by the pacemaker.
Oxygen in the blood exists in an equilibrium. The greater part of the oxygen is attached to the hemoglobin molecules while some part is dissolved in the blood plasma and transported thus through the vascular system including the heart. The amount of oxygen combining with the hemoglobin is dependent on the of oxygen partial pressure in the blood, measurements of either one will give indication as to the amount of oxygen present There are also other factors, which govern the ability of hemoglobin to combine with the oxygen, such as temperature and pH.
The oxygen saturation of the blood, which is a measure of the amount of oxygen bound by the hemoglobin, may be measured by different methods, e.g. transmission photometry and reflection photometry in the venous blood or measured indirectly by electrochemical methods, see above.
The photometric measurements do not show a linear dependency on the oxygen saturation and the measurement values have to be compensated in various ways, which is not the case in the electrochemical methods for measuring the oxygen partial pressure. In these latter methods there is a linear dependency in the measurements of the measured current as a function of the oxygen partial pressure.
The measurements using electro-chemical methods make use of the fact that the oxygen molecules dissolved in the blood are chemically reduced on the surface of the working electrode when the potential during a measurement pulse is forced to negative potential (about 1 volt) relative to a reference electrode/potential. The counter electrode is herein assumed, at least partly, to have a surface made from carbon. In the reduction process, hydroxide ions are produced and the amount of these ions are dependent on the concentration of dissolved oxygen according to the reactions:
at the working electrode 2H2O+O2+4exe2x88x924OHxe2x88x92
at the counter electrode 4OHxe2x88x92xe2x88x92CCO2+2H2O+4exe2x88x92
The above equations show a simplified picture of the process in the liquid (electrolyte), but for the purpose of this description they are sufficient.
The electrical current flowing through the liquid medium to the working electrode during the measurement pulses is carried by the hydroxide ions. This current, called the oxygen current (IpO2), is proportional to the amount of hydroxide ions formed on the surface. During the measurement pulse the carbon coating of the counter electrode is oxidized to minute amounts of carbon dioxide (CO2), which is removed by the blood stream.
Patent documents disclosing different aspects of electro-chemical measurement techniques are, e.g., U.S. Pat. Nos. 4,602,637 and 4,611,604 and 4,779,618 and 4,853,091. A factor influencing these measurements is the drift of the reference electrode.
One of the more stable reference electrodes that may be used is the Ag/AgCL-electrode. However, the bio-compatibility of the reference electrode is important as the reference electrode is to be implanted. Other types of reference electrodes with better bio-compatibility are not as stable as the Ag/AgCl-electrode. The Ag/AgCl-electrode also must be protected by e.g. a membrane when used in vivo because of the above reason.
It is an object of the present invention to improve the stability and sensitivity of an apparatus and a method for making electrochemical measurements by diminishing the effects of the drift of the reference electrode.
Another object of the invention is to increase the overall sensitivity of the measurements.
Another object is to minimize the variations in the amplitude of the measuring current so as to maximize the sensitivity and to diminish possible side effects from currents rising above a certain limit.
Yet another object is reduce as much as possible the amount of energy used for the measuring pulses and still make certain that a relevant value is attained.
The above objects are achieved in accordance with the principles of the present invention in a method and an apparatus for making electrochemical measurements of a concentration of at least one dissolved chemical entity in a liquid medium, employing a counter electrode, a working electrode, and a reference electrode, wherein a measurement potential is applied to the working electrode relative to the reference electrode, corresponding to a measurement voltage, during at least a portion of a measurement period, at which time the dissolved chemical entity participates in an electrochemical reaction at the working electrode resulting in a measurement evoked current, and wherein the measurement evoked current is compared with a predetermined value, and the measurement voltage is decreased or increased in incremental steps so that the measurement current approaches the predetermined value, with the incremental steps being determined by successive comparisons between the successively measured evoked current and the predetermined value.
The invention is based on the observation that during testing of electrodes the measured oxygen current (the current arising as a result of the voltage imposed between the working electrode and the counter electrode) increases or decreases by time. It can, however, be shown that there is an optimal measurement potential where the relative sensitivity is the highest and which decreases on both sides of that optimum.
When the current decreases the sensitivity also decreases because the measurement potential comes closer to the limit beyond which the reduction no longer takes place. On the other hand if the current increases over time the measurement pulse amplitude will have to be reduced since otherwise the risk for tissue stimulation is obvious.
Thus, by continuously adjusting the measurement pulse amplitude compared to the so called reference electrode such that the measurement current IpO2 approaches the predetermined value Iset. Experience from pre-clinical tests has shown that for e.g. a 7 mm2 gold working electrode the measured oxygen current IpO2 should be about 30-80 xcexcA, depending on the area etc. of the working electrode, which will give the optimal results for this material.
The inventive method and the apparatus have several benefits. By keeping the current close to a set value, e.g. in the case of the oxygen-blood system 50 xcexcA, it will be possible to obtain the best sensitivity in the measurements, i.e. the highest variation in the measured current as a function of the physical activity as related to rest.